HIV Management Update 2015

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9/30/15 HIV Management Update 2015 Larry Pineda, PharmD, PhC, BCPS Visiting Assistant Professor Pharmacy Practice and

edu Pharmacist Learning Objectives Describe the HIV life cycle and recognize antiretroviral drug targets Classify an

antiretroviral agents which are recommended for the treatment of HIV+ patients List the antiretroviral agents which

Define HAART Identify the minimum number of antiretroviral drugs in an appropriate HAART regimen Understand the

Retrovirus (RNA) Mature HIV Virion Natural Progression of HIV Two distinct groups: HIV-1, HIV-2 Acquired Immune

1 9/30/15 HIV Management Update 2015 Larry Pineda, PharmD, PhC, BCPS Visiting Assistant Professor Pharmacy Practice and Administrative Science Pharmacist Learning Objectives Describe the HIV life cycle and recognize antiretroviral drug targets Classify an antiretroviral agent by its mechanism of action Summarize pertinent changes to the 2015 DHHS HIV guidelines List the antiretroviral agents which are recommended for the treatment of HIV+ patients List the antiretroviral agents which are recommended for post exposure prophylaxis (PEP) Technician Learning Objectives Human Immunodeficiency Virus (HIV) Define HAART Identify the minimum number of antiretroviral drugs in an appropriate HAART regimen Understand the importance of HAART adherence List the antiretroviral agents which are recommended for post exposure prophylaxis (PEP) Retrovirus (RNA) Mature HIV Virion Natural Progression of HIV Two distinct groups: HIV-1, HIV-2 Acquired Immune Deficiency Syndrome (AIDS) Transmission Sex Injection drug use Perinatal Breast milk HIV/AIDS among leading causes of morbidity/ mortality in U.S. Stage 1 Stage 2 Stage 3 1

2 Epidemiology Late Testers in New Mexico 1.2 million persons 13 years and older living with HIV in U.S ,300 (14%) are unaware of their infection 1 Undiagnosed responsible for over half of new HIV cases 2 Only ~50% of U.S. adults ever tested 3 CDC expanded screening 2006 Annual incidence approximately 50,000 cases 1 Diagnosed in stage % diagnosed with HIV received concurrent AIDS diagnosis Relatively higher than U.S. average 38% Marks G et al. AIDS. 2006;20: Kaiser Family Foundation, 2011 Survey of Americans on HIV/AIDS New Mexico DOH Summer Quarterly Report: July 2010 Living With HIV Early Initiation of Therapy Improves outcomes 1 Prevents progression to AIDS Reduce hospitalizations Decrease risk of opportunistic infections Long healthy life Reduces chance of transmitting to others 2 Undetectable viral load <4% risk Condom use + undetectable viral load <1% risk Campsmith M et al. JAMA 2008;300(5): Kitahata MM et al. N Engl J Med.2009;360(18): Das M et al. PLoS One. 2010;5(6):e11068 HAART What is the minimum number of antiretroviral drugs that should be included in an ideal HIV treatment regimen? A. One B. Two C. Three D. Four E. Five Highly Active Anti-Retroviral Therapy 3 active antiretroviral drugs 2 nucleoside reverse transcriptase inhibitors Plus 3 rd active agent: Integrase strand transfer inhibitor Non-nucleoside reverse transcriptase inhibitor Protease inhibitor with pharmacokinetic enhancer (cobicistat, ritonavir) Adherence critical for success 2

Adherence Goal > 95% What is the percentage of adherence to HAART needed for

> 95% Patterson DL et al. Ann Intern Med.

inhibitor Reverse transcriptase (RT) inhibitors Nucleoside RT inhibitors

inhibitors (INSTI) Protease inhibitors (PI) HIV Life Cycle Entry/Fusion

3 Adherence Goal > 95% What is the percentage of adherence to HAART needed for optimal virologic supression? A. < 70% B % C % D % E. > 95% Patterson DL et al. Ann Intern Med. 2000;133:21-30 The Drugs Antiretroviral Drug Classes Entry inhibitor Fusion inhibitor Reverse transcriptase (RT) inhibitors Nucleoside RT inhibitors (NRTI) Non-nucleoside RT inhibitors (NNRTI) Integrase strand transfer inhibitors (INSTI) Protease inhibitors (PI) HIV Life Cycle Entry/Fusion Inhibitors Selzentry (maraviroc) CCR5-inhibitor Requires tropism assay Fuzeon (enfuvirtide) Subcutaneous injection 3

NRTIs Truvada (tenofovir/emtricitabine) Viread (tenofovir)

(abacavir/lamivudine) Ziagen (abacavir) Epivir (lamivudine)

(zidovudine) NNRTIs Sustiva (efavirenz) Atripla

Complera (rilpivirine/tenofovir/emtricitabine) Viramune

Reyataz (atazanavir) Norvir (ritonavir) Prezcobix

Isentress (raltegravir) Vitekta (elvitegravir) Needs to be

Stribild (elvitegravir/cobicistat/tenofovir/ emtricitabine)

2015 Updated April 2015 5 recommended HAART regimens: 4

ritonavir-boosted protease inhibitor (PI/r)-based regimen 2

4 NRTIs Truvada (tenofovir/emtricitabine) Viread (tenofovir) Emtriva (emtricitabine) Once a day Epzicom (abacavir/lamivudine) Ziagen (abacavir) Epivir (lamivudine) Once a day Combivir (zidovudine/lamivudine) Retrovir (zidovudine) NNRTIs Sustiva (efavirenz) Atripla (efavirenz/tenofovir/emtricitabine) Edurant (rilpivirine) Complera (rilpivirine/tenofovir/emtricitabine) Viramune (nevirapine) Intelence (etravirine) PIs Prezista (darunavir) Reyataz (atazanavir) Norvir (ritonavir) Prezcobix (darunavir/cobicistat) Evotaz (atazanavir/cobicistat) INSTIs Isentress (raltegravir) Vitekta (elvitegravir) Needs to be boosted Tivicay (dolutegravir) Tivicay Stribild Triumeq Stribild (elvitegravir/cobicistat/tenofovir/ emtricitabine) Triumeq (dolutegravir/abacavir/lamivudine) DHHS HIV Guidelines 2015 Updated April recommended HAART regimens: 4 integrase strand transfer inhibitor (INSTI)-based regimens 1 ritonavir-boosted protease inhibitor (PI/r)-based regimen 2 regimens previously categorized as recommended moved to alternative INSTI-Based Regimens Dolutegravir/abacavir/lamivudine (AI) Only if HLA-B*5701 negative Dolutegravir plus tenofovir/emtricitabine (AI) Elvitegravir/cobicistat/tenofovir/emtricitabine (AI) Raltegravir plus tenofovir/emtricitabine (AI) 4

PI-Based Regimen Darunavir/ritonavir + tenofovir/emtricitabine (AI) Atazanavir/ritonavir has been moved to alternative list Alternative List Limitations for use in certain patient populations May be

tenofovir/emtricitabine (BI) Atazanavir/cobicistat* + tenofovir/emtricitabine (BI) Darunavir/ritonavir + abacavir/lamivudine (BII) * Creatinine clearance 70 ml/min Triumeq

cations, separate Prezcobix Darunavir/cobicistat One pill once a day, with food Adverse effects Diarrhea, nausea, vomiting Rash Increased serum creatinine Treatment-naïve only Drug interactions

5 PI-Based Regimen Darunavir/ritonavir + tenofovir/emtricitabine (AI) Atazanavir/ritonavir has been moved to alternative list Alternative List Limitations for use in certain patient populations May be the preferred regimen for some patients NNRTI-based regimens Efavirenz/tenofovir/emtricitabine (BI) Rilpivirine/tenofovir/emtricitabine (BI) PI-based regimens Atazanavir/ritonavir + tenofovir/emtricitabine (BI) Atazanavir/cobicistat* + tenofovir/emtricitabine (BI) Darunavir/ritonavir + abacavir/lamivudine (BII) * Creatinine clearance 70 ml/min Triumeq Dolutegravir/abacavir/lamivudine One pill once a day, with/without food Adverse effects Headache Insomnia Rash, hypersensitivity reaction HLA-B*5701 negative only Drug interactions Polyvalent cations, separate Prezcobix Darunavir/cobicistat One pill once a day, with food Adverse effects Diarrhea, nausea, vomiting Rash Increased serum creatinine Treatment-naïve only Drug interactions CYP-3A4 substrates Evotaz Atazanavir/cobicistat One pill once a day, with food Adverse effects Elevated bilirubin levels, jaundice, scleral icterus Diarrhea, nausea, vomiting Increased serum creatinine Drug interactions CYP-3A4 substrates Tenofovir Alafenamide (TAF) In phase III trials Prodrug of the nucleotide analog tenofovir Conversion occurs intracellulary Lower plasma exposure than tenofovir disoproxil fumarate (TDF) Higher active [drug] in mononuclear cells Benefits over TDF: Less toxicities (nephrotoxicity, BMD/fractures) Smaller dose required (pill size) 5

6 (True/False) All 3 INSTIs are listed as recommended agents in the 2015 DHHS HIV treatment guidelines. A. True B. False Post Exposure Prophylaxis (PEP) Last updated 2013 Elimination of risk stratification for exposure incidents 3-drug PEP regimen for all Expanded list of ARVs for PEP Emphasis on tolerability and convenience of PEP regimen New recommendations for follow-up HIV testing Occupational Risk Exposures Percutaneous injury or contact of mucous membrane or non-intact skin Blood Tissue Body fluids that are potentially infectious CSF, synovial, pleural, pericardial, peritoneal, amniotic, semen, vaginal secretions Not considered infectious:* Feces, nasal secretions, saliva, sputum, sweat, tears, urine, vomitus Toxicity of PEP Regimens Previous PEP boosted PI-based regimens GI side effects common Major reason for not completing PEP Ritonavir has many drug interactions Tolerability major emphasis for recommended PEP Potential side effects should be discussed * Unless visibly bloody HIV PEP Recommendations Newer agents better tolerated and have better toxicity profiles than previous agents 3 or more tolerable agents now recommended for all occupational exposures to HIV 2 NRTIs (backbone) 1 INSTI, ritonavir-boosted PI or NNRTI Other classes may be indicated (resistant virus) To facilitate completion of PEP Optimize side effect and toxicity profiles Optimize dosing convenience Preferred PEP Regimen Raltegravir 400 mg BID + Truvada 1 tab QD 6

Alternative PEP Regimens Timing and Duration of PEP 1 from each column Raltegravir Darunavir + ritonavir Etravirine Rilpivirine Atazanavir + ritonavir Lopinavir/ritonavir Stribild* Tivicay #

7 Alternative PEP Regimens Timing and Duration of PEP 1 from each column Raltegravir Darunavir + ritonavir Etravirine Rilpivirine Atazanavir + ritonavir Lopinavir/ritonavir Stribild* Tivicay # Tenofovir + emtricitabine Tenofovir + lamivudine Zidovudine + lamivudine Zidovudine + emtricitabine Most effective when begun soon after the exposure in animal studies Start as soon as possible after the exposure, preferably within hours (72 hours) Point at which no benefit gained not defined Duration of PEP is full 4 weeks (28 days) * Single tablet daily # Approved 2013 for treatment of HIV s Which of the following statements is TRUE regarding occupational exposure HIV PEP? A. The recommended duration of PEP is 2 weeks B. A positive HIV test is required before initiation of PEP C. An ideal PEP regimen includes abacavir + lamivudine backbone D. PEP should be started as soon as possible after exposure E. Dolutegravir is included as part of the preferred PEP regimen 7

HIV Drugs and the HIV Lifecycle

HIV Drugs and the HIV Lifecycle Together, we can change the course of the HIV epidemic one woman at a time. #onewomanatatime #thewellproject All HIV drugs work by interrupting different steps in HIV's